Molecular markers impacting survival in patients receiving concurrent chemoradiation and Tumor-Treating Fields (TTF) in patients with newly diagnosed glioblastoma: secondary analysis of SPARE trial (P13-13.003)

Abstract

<h3>Objective:</h3> The objective of this study was to evaluate the impact of molecular markers (PTEN, TP53, EGFR, and TERT) on overall survival (OS) and progression-free survival (PFS) of SPARE trial patients. <h3>Background:</h3> SPARE trial (Scalp-sparing radiation with concurrent temozolomide (TMZ) and tumor treating fields; NCT03477110) is a single-arm pilot study that demonstrated the safety and feasibility of concurrent TTF with chemoradiation for newly diagnosed glioblastomas (GBM). <h3>Design/Methods:</h3> This is a secondary analysis of the SPARE trial. Molecular markers of histologically-confirmed, IDH-wildtype GBM patients age ≥ 18 years old with a Karnofsky performance status (KPS) ≥ 60 who received concurrent chemoradiation and TTF followed by maintenance TMZ + TTF were evaluated. Molecular profile was evaluated with next-generation sequencing. Interaction of mutations in PTEN, TP53, EGFR, and TERT with TTF on OS and PFS was evaluated using a multivariable model. <h3>Results:</h3> A total of 30 patients were enrolled in the SPARE trial. 1 patient with IDH-mutant histology was excluded. The median age was 58 (range; 19–77). The median KPS was 90 (range; 70–100). 9 patients (31.0% ) had a methylated MGMT promotor. 14 patients (48.3%) were found to have PTEN mutation, 9 patients (31.0%) with EGFR alteration, 7 (24.1%) with TP53 mutation, and 23 patients (79.3%) with TERT mutated. MGMT methylation remained statistically significant for an increased OS (p=0.032; HR 7.18). TERT had a statistically significant OS benefit (p=0.012; HR 7.60). TERT also showed significant improvement in PFS. However, neither EGFR, TP53, nor PTEN showed any association of PFS or OS for patients who received concurrent TTF and chemoradiation treatment. <h3>Conclusions:</h3> In this secondary analysis, neither EGFR, TP53, nor PTEN mutation showed any association of PFS or OS. However, patients with TERT mutations showed improved OS. Due to the small sample size, further validation studies should be conducted. <b>Disclosure:</b> Ms. Kayne has nothing to disclose. Dr. Poiset has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Niazi has nothing to disclose. Dr. Cappelli has nothing to disclose. The institution of Dr. Alnahhas has received research support from Novocure. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novocure. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zai lab. Dr. Shi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for varian. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novocure.